The invention relates to a novel process for preparing N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides, which are known as intermediates in the preparation of herbicides, to novel N-(2-cyano-4,5-difluoro-phenyl)-sulphonamides and N-(2-cyano-4,5-difluoro-phenyl)-sulphonimides as intermediates for this process and to processes for their preparation.
It is known that certain N-(5-amino-2-cyano-4-fluoro-phenyl)-alkanesulphonamides, such as, for example, N-(5-amino-2-cyano-4-fluoro-phenyl)-methanesulphonamide, are obtained when corresponding halogenated benzene derivatives, such as, for example, 1-amino-4-cyano-2,5-difluoro-benzene, are heated with alkanesulphonamides, such as, for example, methanesulphonamide, in the presence of an acid binder, such as, for example, potassium carbonate, and in the presence of a diluent, such as, for example, N-methyl-pyrrolidone (see EP-A-648772). However, this process affords the desired products in unsatisfactory yields. Accordingly, there is a need for a more favourable preparation process for N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides.
It has now been found that N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula (I) 
in which
R represents in each case optionally substituted alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl
are obtained in high yields and in very good quality when, in a first step, 2-amino-4,5-difluoro-benzonitrile of the formula (II) 
is reacted with sulphonyl halides of the general formula (III)
Xxe2x80x94SO2xe2x80x94Rxe2x80x83xe2x80x83(III)
in which
R is as defined above and
X represents halogen
in the presence of an acid acceptor and in the presence of a diluent at temperatures between 0xc2x0 C. and 150xc2x0 C. and the resulting N-(2-cyano-4,5-difluoro-phenyl)-sulphonamide intermediates of the general formula (IV) and/or N-(2-cyano-4,5-difluoro-phenyl)-sulphonimide intermediates of the general formula (V) 
in which
R is as defined above
are reacted as pure substances or as mixtures in a second step with ammonia in the presence of a diluent at temperatures between 100xc2x0 and 200xc2x0 C.
Surprisingly, the N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula (I) can be obtained by the process according to the invention in a relatively simple manner in high yields and in very good quality, and a pure end product can be prepared via a mixture of intermediates. The intermediates of the formulae (IV) and (V) can be obtained as mixtures in virtually quantitative yield. The main advantage of the process according to the invention is the fact that the use of relatively expensive 2,4,5-trifluoro-benzonitrile can be dispensed with, and the problematic exchange of a fluorine substituent for a sulphonylamino group is not necessary.
The compound 2-amino-4,5-difluoro-benzonitrile of the formula (II) to be used as starting material has not yet been disclosed in the literature; as a novel substance, it also forms part of the subject-matter of the present invention.
The novel compound of the formula (II) is obtained when 4,5-difluoro-2-nitrobenzonitrile of the formula (VI) 
is reacted with a reducing agent which is customary for converting aromatic nitro compounds into the corresponding amino compounds, such as, for example, (a) hydrogen in the presence of a catalyst such as, for example, platinum or palladium (where the two last-mentioned compounds are, if appropriate, xe2x80x9cpoisonedxe2x80x9d and supported on a carrier, such as, for example, activated carbon or barium sulphate), in the presence of a diluent, such as, for example, tetrahydrofuran or dioxane, or (b) metals or metal salts, such as, for example, tin, tin(II) chloride, iron (powder) in the presence of an acid, such as, for example, hydrochloric acid or acetic acid, and, if appropriate, additionally in the presence of a diluent, such as, for example, methanol or ethanol, at temperatures between 0xc2x0 C. and 150xc2x0 C., preferably between 10xc2x0 C. and 100xc2x0 C. (cf. the Preparation Examples).
The intermediates of the formulae (IV) and (V) are not yet known from the literature; as novel substances, they also form part of the subject-matter of the present invention.
The 4,5-difluoro-2-nitro-benzonitrile of the formula (VI) required as precursor is already known (see JP 07070041xe2x80x94cited in Chem. Abstracts 123:111678). According to the patent literature cited, 4,5-difluoro-2-nitro-benzonitrile can be prepared by reaction of 2-bromo-4,5-difluoro-nitrobenzene with copper(I) cyanide in N,N-dimethyl-formamide.
However, the compound of the formula (VI) is also obtained when 3,4-difluorobenzonitrile is reacted with nitric acid, if appropriate in the presence of sulphuric acid, at temperatures between xe2x88x9210xc2x0 C. and +30xc2x0 C. (cf. the Preparation Examples).
Surprisingly, this nitration proceeds in a very uniform manner (regioselectively), and hydrolysis of the cyano group, which is to be expected under the nitration conditions, only occurs to a very low extent.
The formula (III) provides a general definition of the sulphonyl halides further to be used as starting materials in the process according to the invention for preparing N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula (I).
Preferred meanings in the formulae (I), (III), (IV) and (V) are:
R represents in each case optionally halogen-substituted alkyl, alkenyl or alkinyl having in each case up to 6 carbon atoms, represents in each case optionally halogen- or C1-C4-alkyl-substituted cycloalkyl or cycloalkylalkyl having in each case 3 to 6 carbon atoms in the cycloalkyl group and, if appropriate, 1 to 4 carbon atoms in the alkyl moiety, represents in each case optionally nitro-, cyano-, halogen-, C1-C4-alkyl-, C1-C4-halogenoalkyl-, C1-C4-alkoxy-, C1-C4-halogenoalkoxy- or C1-C4-alkoxy-carbonyl-substituted aryl or arylalkyl having 6 or 10 carbon atoms in the aryl group and, if appropriate, 1 to 4 carbon atoms in the alkyl moiety, or represents in each case optionally cyano-, halogen-, C1-C4-alkyl-, C1-C4-halogenoalkyl-, C1-C4-alkoxy- or C1-C4-halogenoalkoxy-substituted heterocyclyl or heterocyclylalkyl having in each case 3 to 5 carbon atoms and 1 to 2 nitrogen atoms and/or one oxygen or sulphur atom in the heterocyclyl group and, if appropriate, 1 to 4 carbon atoms in the alkyl moiety, and
X represents fluorine, chlorine or bromine.
Particularly preferred meanings in the above formulae are:
R represents in each case optionally fluorine- or chlorine-substituted methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, ethenyl, propenyl, butenyl, ethinyl, propinyl or butinyl, represents in each case optionally fluorine-, chlorine-, methyl- or ethyl-substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylniethyl or cyclohexylmethyl, represents in each case optionally nitro-, cyano-, fluorine-, chlorine-, bromine-, methyl-, ethyl-, n- or i-propyl-, n-, i-, s- or t-butyl-, trifluoromethyl-, methoxy-, ethoxy-, n- or i-propoxy-, n-, i-, s- or t-butoxy-, difluoromethoxy-, trifluoromethoxy-, methoxycarbonyl-, ethoxycarbonyl-, n- or i-propoxycarbonyl-substituted phenyl or benzyl, or represents in each case optionally cyano-, fluorine-, chlorine-, bromine-, methyl-, ethyl-, n- or i-propyl-, n-, i-, s- or t-butyl-, trifluoromethyl-, methoxy-, ethoxy-, n- or i-propoxy-, n-, i-, s- or t-butoxy-, difluoromethoxy- or trifluoromethoxy-substituted heterocyclyl from the group consisting of furyl, thienyl, oxazolyl, isoxazolyl, pyrazolyl, pyridinyl and pyrimidinyl, and
X represents chlorine.
The starting materials of the formula (III) are known chemicals for synthesis.
The first step of the process according to the invention for preparing N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula (I) is carried out using an acid acceptor. Suitable acid acceptors are, in general, the customary inorganic or organic bases or acid acceptors. These preferably include alkali metal or alkaline earth metal acetates, amides, carbonates, bicarbonates, hydrides, hydroxides or alkoxides, such as, for example, sodium acetate, potassium acetate or calcium acetate, lithium amide, sodium amide, potassium amide or calcium amide, sodium carbonate, potassium carbonate or calcium carbonate, sodium bicarbonate, potassium bicarbonate or calcium bicarbonate, lithium hydride, sodium hydride, potassium hydride or calcium hydride, lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, sodium methoxide, ethoxide, n- or -i-propoxide, n-, i-, s- or t-butoxide or potassium methoxide, ethoxide, n- or i-propoxide, n-, i-, s- or t-butoxide; furthermore also basic organic nitrogen compounds, such as, for example, trimethylamine, triethylamine, tripropylamine, tributylamine, ethyl-diisopropylamine, N,N-dimethyl-cyclohexylanine, dicyclohexylamine, ethyl-dicyclohexylamine, N,N-dimethyl-aniline, N,N-dimethyl-benzylamine, pyridine, 2-methyl-, 3-methyl-, 4-methyl-, 2,4-dimethyl-, 2,6-dimethyl-, 3,4-dimethyl- and 3,5-dimethyl-pyridine, 5-ethyl-2-methyl-pyridine, 4-dimethylamino-pyridine, N-methyl-piperidine, 1,4-diazabicyclo[2.2.2]-octane (DABCO), 1,5-diazabicyclo[4.3.0]-non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU).
Preferred acid acceptors are basic organic nitrogen compounds.
Suitable diluents for carrying out the first step of the process according to the invention are, especially, inert organic solvents. These include, in particular, aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, benzine, benzene, toluene, xylene, chlorobenzene, dichlorobenzen, petroleum ether, hexane, cycloliexane, dichloromethane, chloroform, carbon tetrachloride; ethers, such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl ether or ethylene glycol diethyl ether; ketones, such as acetone, butanone or methyl isobutyl ketone; nitriles, such as acetonitrile, propionitrile or butyronitrile; amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-formanilide, N-methyl-pyrrolidone or hexamethylphosphoric triamide; esters, such as methyl acetate or ethyl acetate, sulphoxides, such as dimethyl sulphoxide.
Preferred diluents are aprotic polar organic solvents, in particular acetone or acetonitrile, or else basic organic nitrogen compounds, such as pyridine or 5-ethyl-2-methyl-pyridine.
When carrying out the first step of the process according to the invention, the reaction temperatures can be varied within a relatively wide range. In general, the first step is carried out at temperatures between 0xc2x0 C. and 150xc2x0 C., preferably between 10xc2x0 C. and 120xc2x0 C.
The first step of the process according to the invention is generally carried out under atmospheric pressure. However, it is also possible to carry out the process according to the invention under elevated or reduced pressurexe2x80x94generally between 0.1 bar and 10 bar.
For carrying out the first step of the process according to the invention, generally between 1 mol and 10 mol, preferably between 2 mol and 5 mol, of sulphonyl halide of the general formula (III) and between 1 mol and 10 mol, preferably between 2 mol and 5 mol, of acid acceptor are employed per mole of 2-amino-4,5-difluorobenzonitrile of the formula (II).
In a preferred embodiment of the first step of the process according to the invention, the 2-amino-4,5-difluoro-benzonitrile of the formula (II) is initially charged together with an acid acceptor and a diluent, and the sulplionyl halide of the general formula (III) is then slowly metered into this mixture with stirringxe2x80x94and, if appropriate, with cooling. The complete reaction mixture is thenxe2x80x94if appropriate at elevated temperaturexe2x80x94stirred until the reaction has ended.
The mixture of the intermediates of the formulae (IV) and (V)can be worked up in a customary manner. The mixture is, for example, stirred with water or a dilute aqueous acid, the organic phase is separated off, the aqueous phase is, if appropriate, reextracted with an organic solvent which is virtually water-miscible, such as, for example, ethyl acetate, and the combined organic phases are dried and filtered. To isolate the mixture of intermediates, the solvent is carefully distilled off under reduced pressure from the filtrate.
The resulting mixtures of the intermediates of the formulae (IV) and (V)can advantageously be employed without any further purification for the reaction according to the second step of the process according to the invention.
The second step of the process according to the invention is preferably carried out using a diluent. Suitable diluents are, especially, inert organic solvents. These include, in particular, aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, benzine, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform, carbon tetrachloride; ethers, such as diethyl ether, dilsopropyl ether, t-butyl methyl ether, t-pentyl methyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl ether or ethylene glycol diethyl ether; ketones, such as, acetone, butanone or methyl isobutyl ketone; nitrites, such as acetonitrile, propionitrile or butyronitrilc; amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-formanilide, N-methyl-pyrrolidone or hexamethylphosphoric triamide; esters, such as methyl acetate or ethyl acetate, sulphoxides, such as dimethyl sulphoxide.
Preference is given to using, as diluents, aprotic polar organic solvents, in particular diisopropyl ether, t-butyl methyl ether, t-pentyl methyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether or ethylene glycol diethyl ether.
When carrying out the second step of the process according to the invention, the reaction temperatures can be varied within a relatively wide range. In general, the second step is carried out at temperatures between 50xc2x0 C. and 200xc2x0 C., preferably between 100xc2x0 C. and 180xc2x0 C.
The second step of the process according to the invention is generally carried out in a closed reaction vessel (in particular in an autoclave) under elevated pressure, the pressure depending on the set temperature and the solvent used.
For carrying out the second step of the process according to the invention, generally between 1 and 100 mol, preferably between 5 and 50 mol, of ammonia are employed per mole of the sum of the intermediates of the formulae (IV) and (V).
In a preferred embodiment of the second step of the process according to the invention, the reaction components of the formula (IV) and/or (V) are mixed at room temperature (about 20xc2x0 C.) with ammonia and a diluent and heated in a closed reaction vessel until the reaction has ended.
Work-up and isolation of the products of the formula (I)can be carried out by customary methods. The reaction mixture is, for example, filtered after cooling, and the solvent is carefully distilled off under reduced pressure from the filtrate. The product can be obtained in this manner as a residue, generally in good quality.
The compounds of the formula (I) preparable by the process according to the invention can be employed as intermediates for preparing herbicidally active compounds (see EP-A-648749, EP-A-648772, WO-A-95/29158).
The intermediates of the formulae (IV) and (V)can also be used as precursors for preparing herbicides (see EP-A 609734).